The pineapple plant (Ananas comosus) yields several proteolytic enzymes, including bromelain (from the stem and the fruit), ananain, and comosain,¹ as well as several nonproteolytic enzymes such as amylase, peroxidase, and acid phosphatase.² Most bromelain on the market is stem bromelain (which itself is composed of perhaps up to six different types of enzymes, including bromelain A and B).³ Bromelain is widely utilized in food processing to prepare precooked cereals, produce protein hydrolysates, chillproof beer, tenderize meat, etc.; in cosmetics; in diagnostic laboratories; and in pharmaceuticals.

Bromelain is a sulfur-containing enzyme, with an optimum pH activity between 3.0 and 8.0.⁴ Bromelain has endoproteolytic and catalytic activity and predominantly splits peptides, amides, as well as ester bonds involving lysine, alanine, tyrosine, glycine, and other basic amino acids.⁴

The extraction of bromelain is usually accomplished by fractionated ultra-filtration and subsequent lyophilization of the juice pressed from the stem of ripe pineapples (frequently from Ananas comosus of the cayenne variety). The molecular weight varies between 17,800 and 33,000 kDa.

Bromelain activity within the stem of the pineapple can vary widely depending on the age of the plant, as well as on the storage duration and conditions. A Thai study found that 3-year-old peeled pineapple stems contained substantially more activity than second and first year stems as measured in casein digesting units (CDU)—48.76% compared with 32.0% and 19.3%, respectively.⁵ In addition, storage duration before considerable loss of activity occurred was limited to 3 days at room temperature or 2 weeks in a room cooled to 5°C (41°F).⁵

Bromelain Supplements

Over 200 medical articles on bromelain’s therapeutic applications have been published since it was introduced as a therapeutic agent in 1957.^6,⁷ Initially, many studies employed Ananase (Rorer), an enteric-coated bromelain tablet.

Bromelain is currently available in tablets, chewable tablets, capsules, powder, and ointment. Although available in individual enzyme form, supplemental bromelain is often combined with other enzymes, as well as various vitamins, minerals, and herbs, for wider application.

Bromelain activity is measured in “units”—and there are several types of units currently in use. The Food Chemicals Codex recognizes milk-clotting units (MCUs), although gelatin dissolving units (GDU), Federation Internationale du Pharmaceutiques units, and CDUs are also widely utilized. However, these measurement methods are neither interchangeable nor comparable. On the basis of their respective enzyme units, different grades of bromelain are available. Therefore, when purchasing bromelain, be aware of this fact.

Enteral Absorption (or Resorption)

For enzymes to be used systemically, they must reach the circulatory system and be conveyed to needy cells and organs. This means that oral enzymes must pass through the digestive system, into the small intestine, and pass through the brush border into the circulatory system. Further, this is a rationale for enterically coating the enzyme tablets so that they will not be broken down in the digestive tract before they reach the small intestine to pass into the bloodstream. This is also the rationale for consuming enzymes between meals. These enzymes can pass easily through the gut without involvement in food digestion, allowing more enzyme molecules to reach the small intestine, pass through the brush border and into the circulatory system, and be used systemically by needy organs and cells in the body.

In the past, it was widely assumed that large protein molecules—such as enzymes—could not survive the digestive process and be reabsorbed intact. However, numerous studies have demonstrated that bromelain—and other proteolytic enzymes—can be absorbed by the small intestine through a number of routes, pass into the bloodstream, and ultimately circulate throughout the body. Oral administration is effective, as is parenteral administration.⁸^–¹¹

Research on dogs indicated that levels of bromelain (after oral administration) peaked at 10 hours, and were still detectable after 48 hours, whereas intravenous infusion peaked in 50 minutes and was detectable for 5 hours.¹⁰

A randomized, controlled, double-blind study on humans demonstrated that the highest plasma concentration of bromelain was achieved at approximately 48 hours.^12,¹³ A study of 19 men given 3 grams of oral bromelain daily indicated that the enzyme had a plasma half-life of 6 to 9 hours. Researchers estimated that within the 3- to 50-hour period, an average of 10.8 mcg of bromelain was present in plasma.¹³ In both animals and humans, studies indicated that up to 40% of the absorbed orally administered bromelain was absorbed intact.⁹^–¹¹ For an in-depth discussion of enzyme absorption, please refer to Chapter 111 on Pancreatic Enzymes in this book.

Factors Affecting Bromelain Activity

Bromelain, papain (from papaya), and ficin (from figs) are all sulfhydryl proteases and act similarly. Bromelain (from both stem and fruit) is inhibited by metallic ions (including cadmium, copper, iron, lead, and mercury), oxidizing agents (such as iodoacetate, methyl bromide, and hydrogen peroxide), and human serum (both in vivo and in vitro). Cysteine and magnesium activate commercial bromelain.⁸

As with all enzymes, bromelain’s activity can be inhibited by cold or increased by heat. Bromelain is a hydrolytic enzyme, so supplements should be taken with plenty of water to place the enzyme into solution.

Clinical Applications

Bromelain exerts a wide variety of therapeutic effects ⁶^–⁸:

During the process of aging, illness, or injury, the body’s production of pancreatic enzymes decreases in amount, concentration, and potency, thus allowing the growth of pathogenic cells (such as cancer cells). Pathogenic cells are constantly produced by the body; however, the enzymes manufactured by and circulating in the blood lyse the abnormal pathogenic cells, breaking them up and flushing them out of the body. Unfortunately, when weakened through aging, illness, or injury, the body’s capacity to overcome pathogens is diminished, resulting in illness.

Bromelain has long been used to improve digestion. However, when taken systemically, bromelain can also effectively speed healing from inflammatory diseases and conditions; inhibit cancer growth and metastasis; prevent the aggregation of blood platelets, and thereby help to prevent heart attacks, strokes, and other cardiovascular conditions; prevent intestinal attachment of Escherichia coli; improve the symptoms of dysmenorrhea; fight sinusitis; improve burn eschars and speed healing; improve skin appearance; and improve antibiotic and vitamin absorption.

Therefore, systemic enzyme therapy is essential for normal recovery of a sick or injured individual, to augment the body’s own production of pancreatic enzymes, and to stimulate the production of proteolytic enzymes in the pancreas.

Systemic Enzyme Therapy

When taken between meals, enzymes—such as bromelain—move through the digestive system and directly into the small intestine, passing through the brush border into the circulatory system and traveling to the damaged areas. In this way, the enzyme acts systemically. To be most effective, systemically, it is essential to take enzymes on an empty stomach (approximately 1-1/2 hours before or after a meal). However, when used for digestive therapy, enzymes should be ingested before meals (approximately 30 minutes before). See the section on “Dosage” in this chapter.

Aging

Unfortunately, the process of aging is accompanied by an increasingly wide variety of health problems, such as chronic disorders, cancer, cardiovascular disease, and arthritis. Further, the numbers of those over 65 are escalating. According to the U.S. Census Bureau, over 20% of the American population will be age 65 or older by the year 2050. That figure was only 12% in 2008.¹⁴

Most commonly, as it ages, the body loses resiliency and various degenerative diseases manifest, particularly after the age of 50. This is accompanied by a decline in hormone secretion, immune system function, and enzyme production, thus reducing the body’s effectiveness at fighting off foreign invaders. With aging, the body’s enzyme supply also diminishes in activity. The symptoms of aging could be, at least partially, the consequence of these enzymatic reductions. For example, the graying of hair has been attributed to a lack of tyrosinase or a loss of its activity level.

Unlike the known serious side effects of most prescription drugs, bromelain has been shown to effectively fight arthritis, high blood pressure, cancer, and many other disorders associated with aging, but without the serious and long-term side-effects of many drugs.

Bromelain is also effective in fighting the visual signs of aging, including wrinkles. Bromelain is widely incorporated into lotions, creams, scrubs, facial masks, and other skin care products, where it is believed to improve the skin’s appearance by removing dead skin cells.

Cancer

Bromelain delays metastases considerably, delays skin cancer, and is effectively used in adjunctive tumor therapy. There is also some indication that it has a direct effect on cancer cells.¹⁵

The increased understanding of immunology makes it evident that the solution to cancer is not to be found in chemotherapy or radiation therapy, but in the use of immunotherapy (such as systemic enzyme therapy). Pharmacologic and preclinical studies indicate that bromelain acts as an immunomodulator by inducing the production of distinct cytokines (such as interleukin-1β [IL-1β], IL-6, and IL-8, as well as tumor necrosis factor-γ), and by raising the impaired immunocytotoxicity of monocytes against tumor cells.^8,¹⁵^–¹⁹ These findings were recently partially confirmed in mammary tumor patients.¹⁶ Particularly encouraging are animal studies suggesting antimetastatic properties and inhibition of platelet aggregation associated with metastasis, as well as inhibition of invasiveness and growth of tumor cells. It is interesting to note that the antiinvasive activity might not depend on bromelain’s proteolytic activity.^8,^15,¹⁶

An in vitro study on bromelain and glioma (primary brain tumor) cells found that bromelain significantly and reversibly reduced the adhesion, migration, and invasion of glioma cells. Moreover, cell viability was not affected, even after treatment up to 3 months.²⁰

In the United States, skin cancer is the most common form of cancer.²¹ It is generally agreed that exposure to ultraviolet rays increases an individual’s risk of skin cancer. To determine if bromelain could prevent skin cancer, researchers gave hairless mice 20 mg of bromelain per kilogram of body weight per day for 1 year and then subjected them to ultraviolet light for 15 minutes three times per week for the same period.²² After 1 year, only 40% of the bromelain group developed skin cancer (as opposed to 100% of the control group). In addition, it took the bromelain group twice as long to develop lesions. An earlier, 6-month study found that mice receiving 80 mg of bromelain per kilogram of body weight did not develop any abrasions after 2 months.²³

Bromelain (and other proteolytic enzymes) appears useful in the treatment of cancer. A number of mechanisms seem to be responsible. Bromelain had a significant impact on monocytes, natural killer cells, and lymphocytes in a clinical study of 16 women with breast cancer.¹⁶ Regarding monocytic cytotoxicity, some 40% of the patients responded to bromelain with an increase of cytotoxicity from 7.8% to 54% (bMAK-cell activity).